Combined and individual administration of diethyl phthalate and polychlorinated biphenyls and its toxicity in female Wistar rats

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants and known to act as xenoestrogens. PCBs and diethyl phthalate (DEP) are ubiquitous environmental pollutants because both are used as plasticizers and in various other industrial applications. Therefore, a study was undertaken to evaluate the interactive toxicity of DEP and PCBs in young female Wistar rats. Healthy young female albino rats of Wistar strain weighing 100 g (7-8 weeks old) were randomly assigned to five groups of six. each. Group I female rats were fed on normal diet and water ad libitum. Group 11 female rats were maintained on normal diet mixed with corn oil at 16.5 mg/kg diet/day and 0.94 mg/kg body weight/day as oil control. Groups III and IV female rats were given Clophen A60 and DEP dissolved in corn oil mixed with the diet at 50 mg/(kg diet day), which is approximately equal to 2.85 mg/(kg body weight day), individually to each group. Group V female rats received a mixture of DEP and Clophen A60, each dissolved in corn oil mixed with the diet at 50 mg/(kg diet day), which is approximately equal to 2.85 mg/(kg body weight day). Treatment was carried out for 150 days and after the completion of treatment, serum and liver enzymes and other biochemical parameters in the serum and liver were assessed. Liver weight to body weight ratio showed significant increase in Clophen A60 and Clophen A60 + DEP treated rats. In the three treated groups, there was significant decrease in liver glutathione (GSH) and glutathione reductase (GR). Alanine amino transferase (ALT) was significantly increased in the liver of the three treated groups and in the serum of Clophen A60 and DEP alone treated groups and significant decrease only in the serum of Clophen A60 + DEP treated rats. Significant increase in liver and serum lactate dehydrogenase (LDH) and acid phosphatase (ACP) activity was observed in the three treated groups. Alkaline phosphatase (ALP) activity was significantly increased only in the serum of the Clophen A60 and Clophen A60 + DEP treated rats, whereas significant decrease in the serum and liver of DEP alone treated rats was observed. Aspartate aminotransferase (AST) activity and cholesterol levels were highly significant in the liver and serum of DEP treated rats. In addition, cholesterol level was significantly increased in the liver and serum of Clophen A60 treated rats and only in the liver of Clophen A60 + DEP treated rats. Succinate dehydrogenase (SDH) activity was significantly increased in the liver of Clophen A60 and Clophen A60 + DEP treated rats and highly significant increase in the serum of Clophen A60 + DEP treated rats. There was significant increase in triglyceride levels in the liver and serum of Clophen A60 and Clophen A60 + DEP treated rats, whereas significant increase in triglyceride levels in the serum of DEP alone treated rats was observed. Glycogen levels were significantly increased in the liver of Clophen A60 + DEP treated rats, whereas serum glucose levels showed significant decrease, but in Clophen A60 alone treated rats showed significant increase in liver glycogen and serum glucose, whereas DEP alone treated rats showed significant increase in only serum glucose levels. Lipid peroxidation was increased in the liver of DEP treated rats, which was highly significant, compared to significant increase in Clophen A60 and Clophen A60 + DEP treated rats. Histology of liver showed severe vacuolation, loss of hepatic architecture and granular deposits in the hepatocytes of DEP and Clophen A60 + DEP treated rats, whereas in Clophen 60 alone treated rats, hepatocytes showed hyper pigmentation mild loss of hepatic architecture in centrilobular and periportal area. (c) 2005 Elsevier B.V. All rights reserved.